The greater abundances of antibiotic resistance genes (ARGs) in point-of-use tap and reclaimed water than that in freshly treated water raise the question whether residual disinfectants in distribution systems facilitate the spread of ARGs. This study investigated three widely used disinfectants (free chlorine, chloramine, and hydrogen peroxide) on promoting ARGs transfer within Escherichia coli strains and across genera from Escherichia coli to Salmonella typhimurium. The results demonstrated that subinhibitory concentrations (lower than minimum inhibitory concentrations [MICs]) of these disinfectants, namely 0.1-1 mg/L Cl for free chlorine, 0.1-1 mg/L Cl for chloramine, and 0.24-3 mg/L HO, led to concentration-dependent increases in intragenera conjugative transfer by 3.4-6.4, 1.9-7.5, and 1.4-5.4 folds compared with controls, respectively. By comparison, the intergenera conjugative frequencies were slightly increased by approximately 1.4-2.3 folds compared with controls. However, exposure to disinfectants concentrations higher than MICs significantly suppressed conjugative transfer. This study provided evidence and insights into possible underlying mechanisms for enhanced conjugative transfer, which involved intracellular reactive oxygen species formation, SOS response, increased cell membrane permeability, and altered expressions of conjugation-relevant genes. The results suggest that certain oxidative chemicals, such as disinfectants, accelerate ARGs transfer and therefore justify motivations in evaluating disinfection alternatives for controlling antibiotic resistance. This study also triggers questions regarding the potential role of environmental chemicals in the global spread of antibiotic resistance.

The emergence of multidrug-resistant bacteria presents a severe threat to public health and causes extensive losses in livestock husbandry and aquaculture. Effective strategies to control such infections are in high demand. Enhancing host immunity is an ideal strategy with fewer side effects than antibiotics. To explore metabolite candidates, we applied a metabolomics approach to investigate the metabolic profiles of mice after Klebsiella pneumoniae infection. Compared with the mice that died from K. pneumoniae infection, mice that survived the infection displayed elevated levels of l-valine. Our analysis showed that l-valine increased macrophage phagocytosis, thereby reducing the load of pathogens; this effect was not only limited to K. pneumoniae but also included Escherichia coli clinical isolates in infected tissues. Two mechanisms are involved in this process: l-valine activating the PI3K/Akt1 pathway and promoting NO production through the inhibition of arginase activity. The NO precursor l-arginine is necessary for l-valine-stimulated macrophage phagocytosis. The valine-arginine combination therapy effectively killed K. pneumoniae and exerted similar effects in other Gram-negative (E. coli and Pseudomonas aeruginosa) and Gram-positive (Staphylococcus aureus) bacteria. Our study extends the role of metabolism in innate immunity and develops the possibility of employing the metabolic modulator-mediated innate immunity as a therapy for bacterial infections.

Proper diagnosis and treatment are unavailable to many dementia patients because of a lack of dementia doctors and memory clinics in China.

Breast cancer is a complex disease driven by multiple factors including both genetic and epigenetic alterations. Recent studies revealed that abnormal gene expression induced by epigenetic changes, including aberrant promoter methylation and histone modification, plays a critical role in human breast Carcinogenesis. Silencing of tumor suppressor genes (TSGs) by promoter CpG methylation facilitates cells growth and survival advantages and further results in tumor initiation and progression, thus directly contributing to breast tumorigenesis. Usually, aberrant promoter methylation of TSGs, which can be reversed by pharmacological reagents, occurs at the early stage of tumorigenesis and therefore may serve as a potential tumor marker for early diagnosis and therapeutic targeting of breast cancer. In this review, we summarize the epigenetic changes of multiple TSGs involved in breast pathogenesis and their potential clinical applications as tumor markers for early detection and treatment of breast cancer.